1. Field of the Invention
The invention relates to a zirconium-free neutral glass having a low boron oxide content and good hydrolytic stability for preferential use in the pharmaceutical sector.
2. Description of Related Art
In the pharmaceutical sector and for diagnostic and cosmetic applications, glass is employed as a packaging material on a large scale. Particularly the specific material properties thereof, such as high transparency, good mechanical properties and low permeability, in conjunction with good chemical stability, are crucial for the retention of the quality of medicaments, for example, and the efficacy thereof.
Containers for pharmaceutical, therapeutic, diagnostic and cosmetic purposes are generally in direct contact with the active ingredient contained therein and are therefore subject to strict demands. The containers, which may take the form, for example, of vials, ampoules, syringes or carpules, are therefore also referred to as primary packaging. During the storage of the active ingredients in the primary packaging, minimum loss of and no change in the active ingredients should occur. The quality of the contents must not be altered by direct contact with the primary packaging in such a way as to exceed the verified and stipulated limits. In each case, it has to be ensured that the glass material does not release any substances in amounts that impair the stability of the active ingredient or could even be toxic or harmful to a user in any other way.
Medicaments and other active ingredients are usually processed further and stored in dissolved form, especially on an aqueous basis. A particularly important property of a primary packaging made of glass is therefore the stability of the inner surface that comes into direct contact with the dissolved active ingredient and can be attacked thereby. This can cause various ions to be leached out of the glass surface and adversely affect the contents and active ingredient present therein. In order to rule out losses of action and especially health risks, therefore, generally as small an amount as possible of ions should be leached out of the glass. Since water-based solvents are the most commonly used, hydrolytic stability in particular is an important demand for the use of a glass as primary packaging. For acidic or basic solutions, corresponding demands on acid stability and alkali stability of the material of the packaging should be noted.
Hydrolytic class is also a basis for the classification of glass types for pharmaceutical uses according to the European Pharmacopoeia. Commonly used glasses are divided into classes. What are called type I glasses belong to hydrolytic class 1 and are also referred to as neutral glass. These also include the borosilicate glasses, which contain significant amounts of boron oxides, aluminium oxides or alkaline earth metal oxides.
It is known that an addition or increase in the proportion of boron oxide frequently leads to an improvement in hydrolytic stability, to lowering of the viscosity of the glass melt and to a reduction in the coefficient of expansion. Since these properties are particularly welcome for use as primary packaging in particular, the known glasses contain comparatively high boron oxide contents (up to 20%). Boron binds the alkali metal ions present more firmly into the glass structure. Because of the discovery that boron oxide is harmful to health, however, this concept is no longer justifiable. Boron oxide as an isolated substance is suspected of being teratogenic. This is of particular relevance for the production process of a glass, since complex health and safety measures are required when working with boron oxide as a starting component, and these increase the production costs of the end product. Boron components leached out of a glass could have an influence of toxicological concern on lifeforms.
Low-boron oxide (neutral) glasses are already known.
DE 4430710 C1 discloses a low-boric acid borosilicate glass having high chemical stability with the following composition in % by weight based on oxide:
SiO2>75,B2O31-<9,Al2O33-6,Li2O0-4,Na2O0-8,K2O0-6,MgO0-3,CaO0-3,BaO0-2,SrO0-2,ZnO0-3,ZrO20-3,SnO20-3,SnO0-3,TiO20-2,CeO20-2, andFe2O30-1, whereinSiO2 + B2O3>83,SiO2: B2O3 >8,SiO2 + Al2O3 + ZrO2>83,Li2O + Na2O + K2O5-10, andMgO + CaO + BaO + SrO + ZnO ≤3.
According to the information in DE 4430710 C1, the glasses specified in the examples attain hydrolytic class HBK1 (according to the obsolete DIN 12111). However, determinations conducted in the context of the invention by the more modern method according to the United States Pharmacopeia (USP, see below) showed that the glass examples disclosed, in respect of the limit for hydrolytic class 1, are only in the moderate range and are therefore not competitive pharmaceutical glasses. Chemical stability is achieved in the glass examples described by means of high contents of zirconium oxide/ZrO2 (up to 1.6% by weight) and/or relatively high boron oxide contents (up to 8.9% by weight).
The alkali metal content reported in the glass compositions specified by way of example is almost exclusively sodium oxide and lithium oxide. The sodium oxide content in the examples is above the inventive range. Potassium oxide is used only in example 5, but here in conjunction with a content of lithium oxide well above the inventive limit and a high zirconium oxide content. Measurements in the context of this invention have shown that such a composition gives rise to glasses having relatively poor values within the hydrolytic class HBK1 (high alkali metal ion release).
According to the disclosure of DE102010029975 A1, a low-boron oxide borosilicate glass having the following composition (in % by weight based on oxide) is described:
SiO2 70-79,B2O3  0-<5,Al2O3  1-<5,ZrO20.5-<5,TiO20.5-6,Na2O  1-6,K2O  3-8, andLi2O  0-0.5, whereinSiO2 +B2O3<83.
To achieve the hydrolytic stability, the neutral glasses described therein necessarily contain zirconium oxide and titanium oxide in balanced mass ratios. The zirconium content here is also coupled to the potassium content, in order to establish the physical and chemical properties of the compositions. The good chemical properties of these glasses are attributed to the required content of zirconium oxide, titanium oxide and potassium oxide, and the interaction thereof in the glass.
It is known that zirconium oxide as a stabilizing additive promotes the chemical stability of glasses. It is used specifically for that purpose in DE 4430710 C1 and DE 102010029975 A1. To increase hydrolytic stability, it is used in DE 102010029975 A1 as a necessarily required constituent in combination with titanium oxide and in combination with potassium oxide in specific ratios for achievement of a synergistic effect. However, zirconium as a constituent of a neutral glass in the pharmaceutical sector is problematic, since these glasses require special approval and zirconium can be an unwanted constituent because it can include, inter alia, small amounts of uranium oxides and other radioactive substances (e.g. thorium compounds).